Rapid advances in technology, are leading to field-deployable mobile sensing devices that can now be used to quantify the complex dynamics across time of key physical, biological, behavioral, social, and environmental factors that contribute to health and disease risk. These data will enable us to break through to the next level of biomedical understanding of causation in complex disorders. While ongoing efforts have made significant strides in the analysis of big data in the areas of genomics, imaging, and EHR, significant new investment is needed to develop and disseminate data analytics tools specific to the unique features of mobile sensor data (e.g., high volume, velocity, variety, variability, and versatility) to convert this wealth of data into information, knowledge, and action. Investment in a strong, open, scientific, and computational infrastructure for mobile big data at this early stage promises outsize returns to advance science and improve health. The Data Science Research (DSR) Core of the Center of Excellence for Mobile Sensor Data to Knowledge (MD2K) will generate generalizable theory, methods, tools, and software, to address major barriers to processing complex mobile sensor data (e.g., transition from early lab feasibility to robust field utility) so as to enable the use of mobile sensor data by the broader community for biomedical knowledge discovery and just-in-time care delivery, laying the foundation for P5 Medicine. The DSR Core will demonstrate the feasibility, utility, and generalizability of the MD2K approach by implementing the entire MD2K data analytics system in the context of two biomedical applications - reducing relapse among abstinent daily smokers and reducing readmission among congestive heart failure (CHF) patients. All the tools and software developed by MD2K will be freely available as open-source projects to engage data science researchers in advancing the science of MD2K. Biomedical researchers will be able to install the MD2K software on mobile devices to collect mobile sensor data and the MD2K analytics software on their servers to analyze these data for biomedical discovery.